Prostaglandin E₂ regulates renal function in C57/BL6 mouse with 5/6 nephrectomy

To investigate the roles of cyclooxygenases (COX) and their metabolites in C57/BL6 mice with 5/6 nephrectomy, an animal model of chronic renal failure.

C57/BL6 mice were grouped into sham-operated (2K), one kidney removal (1K) and 5/6 nephrectomy groups (5/6Nx). Renal resistive index was measured by ultrasonography. Blood, aortae, renal arteries and renal cortex were collected for measurement of kidney function, assessment of vascular responsiveness, Western blotting, immuohistochemistry and enzyme-linked immunosorbent assays.

After four weeks, acetylcholine-induced relaxations were blunted in renal arteries of 1K and 5/6Nx mice; indomethacin, a non-selective COX inhibitor, improved the response in 5/6Nx, but not in 1K renal arteries. In 5/6Nx renal arteries, but not in 1K preparations, the protein presence of endothelial nitric oxide synthase (eNOS) was decreased, while that of COX-2 and its products [prostacyclin and thromboxane A₂] were increased. The renal resistive index was lower in 5/6Nx mice, suggesting a lower resistance in the renal microvasculature. In the renal cortex of 5/6Nx mice, eNOS protein presence was increased; while the presence of COX-2 was not detectable. The prostaglandin E₂ level was lower in the 5/6Nx cortex than in the other two groups.

The early stage of renal mass removal is associated with increased renal arterial constriction and reduced microvascular resistance. The former is due to downregulation of eNOS and upregulation of COX-2, leading to an increased production of prostacyclin and thromboxane A₂. A reduced production of PGE₂ in the renal cortex is important for maintaining normal renal function.